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Publication Abstract from PubMed

Metabotropic glutamate receptors belong to a family of G protein-coupled receptors that are obligate dimers and possess a large extracellular ligand-binding domain that is linked via a cysteine-rich domain to their 7-transmembrane domain(1). Upon activation, these receptors undergo a large conformational change to transmit the ligand binding signal from the extracellular ligand-binding domain to the G protein-coupling 7-transmembrane domain(2). In this manuscript, we propose a model for a sequential, multistep activation mechanism of metabotropic glutamate receptor subtype 5. We present a series of structures in lipid nanodiscs, from inactive to fully active, including agonist-bound intermediate states. Further, using bulk and single-molecule fluorescence imaging, we reveal distinct receptor conformations upon allosteric modulator and G protein binding.

Stepwise activation of a metabotropic glutamate receptor.,Krishna Kumar K, Wang H, Habrian C, Latorraca NR, Xu J, O'Brien ES, Zhang C, Montabana E, Koehl A, Marqusee S, Isacoff EY, Kobilka BK Nature. 2024 May;629(8013):951-956. doi: 10.1038/s41586-024-07327-x. Epub 2024 , Apr 17. PMID:38632403^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.